The invention relates to the use of heptapeptide somatostatin derivatives and peptidomimetics selected therefrom by computerized artificial intelligence software on the basis of chemical similarity for the preparation of pharmaceutical compositions with neurogenic or non-neurogenic anti-inflammatory as well as analgetic effects.
It is known that somatostatin, a tetradecapeptide occurring in the nature and its synthetic analogues inhibit the release of the growth hormone and in addition, they inhibit or control, respectively, a number of other endocrine secretions (e.g. glucagon, insulin, gastrin, prolactin, secretin, cholecystokinin) and cellular functions, too [Reichlin, D.: Somatostatin. N. Engl. J. Med., 309, 1495-1501 (1983)]. It is also known from the literature that, simultaneously with the above endocrine effects, somatostatin and a significant number of its known analogues exhibit also a rather strong inhibitory effect on the cellular growth [Schally, A. V.: Cancer Res. 48, 6977-6985 (1988); U.S. Pat. No. 4,650,787; European patent specifications Nos. 0,215,171 and 0,175,644]. The therapeutical utilization of both the natural hormone and the above analogues is significantly limited by their broad spectrum of activity. Thus, the treatment of various clinical pictures could be considerably improved by selectively acting analogues.
It is also known that compounds of formula (I) 
represent the single group of selectively acting somatostatin peptide analogues. These compounds very strongly inhibit the division of tumorous cells both under in vitro and in vivo conditions but do not show the endocrine effects of somatostatin or other known peptide analogues [Kxc3xa9ri, Gy.: Biochem. Res. Comm. 191, 681-687 (1993); U.S. Pat. No. 5,480,870].
Furthermore, it is known that certain compounds of low molecular weight, namely the so-called xe2x80x9cpeptidomimeticsxe2x80x9d carrying functional groups characteristic of a given peptide are capable to undergo an interaction with the peptide receptors and thereby to exert a biological action similar to that of the peptide. The compounds of formula (II) 
are known to strongly inhibit the division of tumour cells similarly to somatostatin analogues (Hungarian patent specification No. 214,061).
It is also known that all inflammatory processes occurring in the organism include more or less neurogenic components. An outstanding importance is attributed to the neurogenic inflammation in the pathomechanism of the following diseases:
a) Inflammations of chiefly allergic origin in the mucous membranes of airways: rhinitis, bronchitis and bronchial asthma;
b) arthritises;
c) allergic conjuctivitis, urticaria;
d) inflammations of the gastrointestinal system, colitis;
e) psoriasis.
At present, no drug is known which could reliably inhibit the neurogenic inflammations, thereby providing the possibility of an efficient treatment of the above pathological pictures. There have been carried out for ages investigations connected with the classic non-steroidal anti-inflammatory drugs but none of the investigated sodium salicylate (250 mg/kg i.v.), amidopyridine (200 mg/kg p.o.), phenylbutazone (100 mg/kg i.v.), flufenamic acid (20 mg/kg i.v.), or indomethacin (10 mg/kg p.o.) exhibited any significant inhibitory effect. Steroids inhibit the neurogenic inflammation in such high doses, which induce toxic effects. Opiates alone proved to be effective, but their practical use cannot be taken into consideration because of the danger of several side effects [Szolcsxc3xa1nyi, J.: Neurogenic inflammation: reevaluation of axon reflex theory. In: Neurogenic Inflammation. P. Gepetti and P. Holzer (eds.), CRP Press, Boca Raton Fl. 35-44 (1996); Capsaicin and neurogenic inflammation: History and early findings. In: Antidromic vasodilataton and neurogenic inflammation. L. A. Chahl and J. Szolcsxc3xa1nyi: Systemic anti-inflammatory effect induced by antidromic stimulation of the dorsal roots in the rat. Neuroscience Letters 212, 1-4 (1996)].
It had been proven in earlier studies that the pretreatment with somatostatin prevented the experimentally induced neurogenic inflammation, but because of its broad spectrum of activities (endocrine action, modulation of cardiovascular and gastrointestinal functions, influence on cognitive and behavioural processes) and its short half life, it cannot be taken into account from a therapeutical point of view.
It has been shown that somatostatin can be found in the peripheral endings of capsaicin-sensitive primary afferent neurons (CSPAN) and is liberated on the effect of stimulation. Capsaicin (8-methyl-N-vanillyl-6-nonene amide), the pungent substance of red pepper, selectively stimulates or, in high doses, selectively stimulates a subgroup of primary afferent neurons (small, dark nerve cells of type B). On the basis of this property, this subpopulation of neurons is recorded under the name xe2x80x9ccapsaicin-sensitive primary afferent neurons) (CSPAN) in the literature [Szolcsxc3xa1nyi, J., Pxc3x3rszxc3xa1sz, R., Pethxc3x6, G.: Capsaicin and pharmacology of nociceptors. In: Peripheral neurons in nociception: physio-pharmacological aspects. J. M. Besson, G. Gialbaud, I. Ollat (eds.), John Libbey, Eurotext, Paris 109-124 (1994); Maggi, C. A.: Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Progr. Neurobiol. 45, 1-98 (1995)]. Capsaicin-sensitive primary sensory neurons form about one half of the nerve cell population of sensory ganglions. This group includes the C-polymodal nociceptors amounting to about 60 to 70% of C-afferentation of the skin as well as the perivascular chemoceptive interoceptors of the mucous membranes (conjunctiva, airways, urogenital system, etc.) and visceral organs (heart, kidney, stomach etc.), which can be excited by chemical painstimuli (bradykinin, acids, capsaicin). A common property of these nociceptive afferents without unmedullated fibres or with a thin myelin sheath of A-delta fibre range is that, under the effect of stimuli, tachykinins (P substance, neurokinin A), calcitonin gene-related peptide (CGRP) [C. A. Maggi: Tachykinins and calcitonin gene related peptide (CGRP) as cotransmitters released from peripheral endings of sensory nerves. Progress in Neurobiology 45, 1-98 (1995)] and somatostatin are released from their peripheral endings. Tachykinins induce plasma extravasation and neurogenic inflammation on the venules whereas CGRP gives rise chiefly to vasodilatation of the arterioles and enhancement of microcirculation [L. A. Chahl: Antidromic vasodilatation and neurogenic inflammation. Pharmacol. Ther. 37, 275-300 (1988)]. Thus, the capsaicin-sensitive peptidergic sensory nerve endings and terminal varicosities equally provide both a nociceptive afferent function as well as an efferent function eliciting a local tissue response. They play an important role in the signalling of neuropathic or inflammatory as well as hot stimulus- or irritant-induced pains [Szolcsxc3xa1nyi, J.: Actions of capsaicin on sensory receptors. In: Capsaicin in the Study of Pain, J. N. Wood (ed.), Academic Press, London 1-26 (1993)].
The aim of the invention is to develop pharmaceutical compositions, which are equally useful to inhibit both neurogenic and non-neurogenic inflammations as well as to alleviate pain.